Is ANK2 p.Ser1402= (c.4206T>C) pathogenic?

ANK2 p.Ser1402= (c.4206T>C) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ser1402= (c.4206T>C)?

ANK2 p.Ser1402= (c.4206T>C) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is ANK2 p.Ser1402= (c.4206T>C) in the general population?

ANK2 p.Ser1402= (c.4206T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

ANK2 p.Ser1402=

c.4206T>C · rs769675138 · VCV668177

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.121	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.053	GERP -5.5, phastCons 0.97
Overall
CADD	8.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,902 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,226 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,451
European (non-Finnish)	0.000678%	147,425

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANK2
Protein: p.Ser1402=
Coding: c.4206T>C
MANE Select: NM_001148
dbSNP: rs769675138
Type: single nucleotide variant
Location: chr4:113343100 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1402: a β-strand; the 'upa domain' region

Full ANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome

Similar variants

ANK2 p.Ser1402Arg Uncertain significance ★ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>T Uncertain significance ★★ same condition
ANK2 c.2079+5T>G Uncertain significance ★★ same condition
ANK2 c.2278-3C>T Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ank2-p-ser1402 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown